An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure.

Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1. Although some pharmacologic inhibitors of P-gp and OATP1B1 increase edoxaban exposure, neither the ABCB1 C3435T nor the SLCO1B1 T521C polymorphism affected edoxaban PK. A slight elevation in M4 exposure was observed among SLCO1B1 C-allele carriers; however, this elevation is unlikely to be clinically significant as plasma M4 concentrations comprise <10% of total edoxaban levels.

Factors Associated with Anxiety About Colonoscopy: The Preparation, the Procedure, and the Anticipated Findings.

BACKGROUND: Previous research has assessed anxiety around colonoscopy procedures, but has not considered anxiety related to different aspects related to the colonoscopy process. AIMS: Before colonoscopy, we assessed anxiety about: bowel preparation, the procedure, and the anticipated results. We evaluated associations between patient characteristics and anxiety in each area. METHODS: An anonymous survey was distributed to patients immediately prior to their outpatient colonoscopy in six hospitals and two ambulatory care centers in Winnipeg, Canada. Anxiety was assessed using a visual analog scale. For each aspect, logistic regression models were used to explore associations between patient characteristics and high anxiety. RESULTS: A total of 1316 respondents completed the questions about anxiety (52% female, median age 56 years). Anxiety scores > 70 (high anxiety) were reported by 18% about bowel preparation, 29% about the procedure, and 28% about the procedure results. High anxiety about bowel preparation was associated with female sex, perceived unclear instructions, unfinished laxative, and no previous colonoscopies. High anxiety about the procedure was associated with female sex, no previous colonoscopies, and confusing instructions. High anxiety about the results was associated with symptoms as an indication for colonoscopy and instructions perceived as confusing. CONCLUSIONS: Fewer people had high anxiety about preparation than about the procedure and findings of the procedure. There are unique predictors of anxiety about each colonoscopy aspect. Understanding the nuanced differences in aspects of anxiety may help to design strategies to reduce anxiety, leading to improved acceptance of the procedure, compliance with preparation instructions, and less discomfort with the procedure.

Living gluten-free: adherence, knowledge, lifestyle adaptations and feelings towards a gluten-free diet.

BACKGROUND: A gluten-free diet (GFD) requires tremendous dedication, involving substantive changes to diet and lifestyle that may have a significant impact upon quality of life. The present study aimed io assess dietary adherence, knowledge of a GFD, and the emotional and lifestyle impact of a GFD. METHODS: Community dwelling adults following a GFD completed a questionnaire with items related to reasons for avoiding gluten, diagnostic testing, GFD adherence, knowledge and sources of information about a GFD, the Work and Social Adjustment Scale, and the effect of a GFD diet on lifestyle, feelings and behaviours. RESULTS: Strict GFD adherence among the 222 coeliac disease (CD) patients was 56%. Non-CD individuals (n = 38) were more likely to intentionally ingest gluten (odds ratio = 3.7; 95% confidence interval = 1.4-9.4). The adverse impact of a GFD was modest but most pronounced in the social domain. Eating shifted from the public to the domestic sphere and there were feelings of social isolation. Affective responses reflected resilience because acceptance and relief were experienced more commonly than anxiety or anger. Non-CD respondents were less knowledgeable and less likely to consult health professionals. They experienced less anger and depression and greater pleasure in eating than CD respondents. CONCLUSIONS: The findings obtained in the present suggest there is good potential for positive adaptation to the demands of a GFD; nevertheless, there is a measurable degree of social impairment that merits further study. The GFD may be a viable treatment option for conditions other than CD; however, education strategies regarding the need for diagnostic testing to exclude CD are required.

Animal movement on the hoof and on the cart and its implications for understanding exchange within the Indus Civilisation.

Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling.

BACKGROUND: Tamoxifen is commonly used for breast cancer therapy. However, tamoxifen resistance is an important clinical problem. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug-resistant cancer progenitors. METHODS: To investigate signalling mechanisms important for the maintenance and viability of drug-resistant cancer progenitors, we used microarray analysis, PCR array for genes involved in cancer drug resistance and metabolism, flow cytometry, soft agar colony formation assay, in vivo tumourigenicity assay and immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant breast cancer MCF7 cells. RESULTS: Downregulation of CXCR4 signalling by small molecule antagonist AMD3100 specifically inhibits growth of progenitor cell population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours treated with AMD3100. Further, small molecule antagonists of AhR signalling specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of MCF7(TAM-R) xenografts in vivo. CONCLUSION: The chemokine receptor CXCR4 maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells through AhR signalling and could be a putative target for the treatment of tamoxifen-resistant breast cancers.

Bacteriophages in live virus vaccines: lack of evidence for effects on the genome of rhesus monkeys.

Four juvenile rhesus monkeys were inoculated with 10(12) plaque-forming units of the bacteriophage phiV1 isolated from live virus vaccines. After phiV1 had been cleared from the blood, DNA's were isolated from the livers and kidneys and analyzed for the presence of bacteriophage by plaque assays, and for the presence of phiV1 DNA by DNA-DNA reassociation kinetics. No evidence was found for persistence of the bacteriophage or for replication of the phage genome in these rhesus monkeys.

Expression of the Escherichia coli cell division gene sep cloned in a lambda Charon phage.

The Escherichia coli cell division gene sep, which probably codes for one of the penicillin-binding proteins, has been cloned into lambda Charon 10 to form a viable sep+ transducing phage. After infection with this hybrid phage, penicillin-binding protein 3 was overproduced and incorporated into the E. coli inner membrane.

Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

AIMS: After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. METHODS: Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. RESULTS: We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). CONCLUSION: The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Independent Validation of a Self-Report Version of the IBD Disability Index (IBDDI) in a Population-Based Cohort of IBD Patients.

Introduction: A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate the IBDDI in a North American setting and adapt for use as a self-report tool. Methods: Persons 18-65 years old from the population-based University of Manitoba IBD Research Registry were mailed a self-administered survey. This survey included the IBDDI and several scales that should correlate with a disability measure- the World Health Organization (WHO) Disability Assessment Scale (WHODAS) 2.0, Work and Social Adjustment Scale (WSAS), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the K6-Kessler Emotional Distress Scale. We used Pearson correlation coefficients to assess construct validity, Cronbach's alpha to assess internal consistency, and Factor analysis to assess which of the IBDDI items likely belonged to a single IBD-related disability factor. Results: In response to the survey request,1143 (46% of those contacted) participated (61% female, mean age 51, 52% with Crohn's disease). On an index scale from 0-100, 14% had a score ≥50 (extreme disability, 18% of those with Crohn's disease; 10% of those with ulcerative colitis). There were strong correlations between IBDDI and WSAS (0.76), WHODAS (0.76), K6 (0.73), and an inverse correlation with IBDQ (-0.86). The Cronbach's alpha was high (0.88). All but 2 items (number of liquid stools in the past week and arthritis/arthralgia) of the 14 identified for IBDDI loaded highly onto a single factor (factor loading > 0.40). Conclusions: The findings support the validity of this new self-report version of the IBDDI as a sound measure of disability in IBD.

Predictors of patient reluctance to wake early in the morning for bowel preparation for colonoscopy: a precolonoscopy survey in city-wide practice.

INTRODUCTION: Many endoscopists do not use split-dose bowel preparation (SDBP) for morning colonoscopies. Despite SDBP being recommended practice, they believe patients will not agree to take early morning bowel preparation (BP). We assessed patients' opinions about waking early for BP. METHODS: A self-administered survey was distributed between 08/2015 and 06/2016 to patients in Winnipeg, Canada when they attended an outpatient colonoscopy. Logistic regression was performed to determine predictors of reluctance to use early morning BP. RESULTS: Of the 1336 respondents (52 % female, median age 57 years), 33 % had used SDBP for their current colonoscopy. Of the 1336, 49 % were willing, 24 % neutral, and 27 % reluctant to do early morning BP. Predictors of reluctant versus willing were number of prior colonoscopies (OR 1.20; 95 %CI: 1.07 - 1.35), female gender (OR 1.65; 95 %CI: 1.19 - 2.29), unclear BP information (OR 1.86; 95 %CI: 1.21 - 2.85), high BP anxiety (OR 2.02; 95 %CI: 1.35 - 3.02), purpose of current colonoscopy being bowel symptoms (OR 1.40; 95 %CI: 1.00 - 1.97), use of 4 L of polyethylene glycol laxative (OR 1.45; 95 %CI: 1.02 - 2.06), not having SDBP (OR 1.96; 95 %CI: 1.31 - 2.93), and not having finished the laxative for the current colonoscopy (OR 1.66; 95 %CI: 1.01 - 2.73). Most of the same predictors were identified when reluctance was compared to willing or neutral, and in ordinal logistic regression. CONCLUSIONS: Almost three-quarters of patients do not express reluctance to get up early for BP. Among those who are reluctant, improving BP information, allaying BP-related anxiety, and use of low volume BP may increase acceptance of SDBP.

Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten-free diet.

BACKGROUND: A gluten-free diet is the only recommended treatment for coeliac disease. AIM: To determine the prevalence and characteristics of reactions to gluten among persons with coeliac disease on a gluten-free diet. METHODS: Adults with biopsy proven, newly diagnosed coeliac disease were prospectively enrolled. A survey related to diet adherence and reactions to gluten was completed at study entry and 6 months. The Coeliac Symptom Index, Coeliac Diet Assessment Tool (CDAT) and Gluten-Free Eating Assessment Tool (GF-EAT) were used to measure coeliac disease symptoms and gluten-free diet adherence. RESULTS: Of the 105 participants, 91% reported gluten exposure <1 per month and median CDAT score was 9 (IQR 8-11), consistent with adequate adherence. A suspected symptomatic reaction to gluten was reported by 66%. Gluten consumption was unsuspected until a reaction occurred (63%) or resulted from problems ordering in a restaurant (29%). The amount of gluten consumed ranged from cross-contact (30%) to a major ingredient (10%). Median time to symptom onset was 1 h (range 10 min to 48 h), and median symptom duration was 24 h (range 1 h to 8 days). Common symptoms included abdominal pain (80%), diarrhoea (52%), fatigue (33%), headache (30%) and irritability (29%). CONCLUSIONS: Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten-free diet. Eating at restaurants and other peoples' homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten-free diet adherence.

Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis.

BACKGROUND: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. OBJECTIVE: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. METHODS: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. RESULTS: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, -0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. CONCLUSION: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.

Isolation and characterization of dnaX and dnaY temperature-sensitive mutants of Escherichia coli.

Escherichia coli mutants with temperature-sensitive (ts) mutations in dnaX and dnaY genes have been isolated. Based on transduction by phage P1, dnaX and Y have been mapped at minutes 10.4--10.5 and 12.1, respectively, in the sequence dnaX purE dnaY. Both dna Xts36 and Yts10 are recessive to wild-type alleles present on episomes. F13 carries both dnaX+ and Y+; the shorter F210 carries dnaY+, but not X+. Lambda tranducing phages that carry dnaX+ or Y+ have been isolated, and hybrid plasmids of Col E1 and E. coli DNA from the Clarke and Carbon (1976) collection also carry portions of the dnaX purE dnaY region. Results obtained with the lambda transducing phages and the hybrid plasmids suggest that dnaX is a different gene from the previously characterized dnaZ gene, which is also near minute 10.5--The dnaXts36 mutant, after a shift to 42 degrees, stopped DNA synthesis gradually, and the total amount of DNA increased two-fold. When this mutant was shifted to 44 degrees, the rate of DNA synthesis dropped immediately and the final increment of DNA was only 10% of the initial amount. Replicative DNA synthesis in toluene-treated cells was completely inhibited at 42 degrees and was partially inhibited even at 30 degrees.--When the dnaYts10 mutant was shifted to 42 degrees, DNA synthesis gradually stopped, and the amount of DNA increased 3.6-fold. At 44 degrees, residual DNA synthesis amounted to a two-fold increase. Replicative DNA synthesis in vitro in toluene-treated cells was inactivated after 20 minutes at 42 degrees or by "preincubation" of cells at 42 degrees before toluene treatment.--The dnaX and dnaY products probably function in polymerization of DNA, although participation also in initiation cannot be excluded.

Social phobia symptoms, subtypes, and severity: findings from a community survey.

OBJECTIVES: Our goals were (1) to ascertain the range of functional impairment attributable to social phobia in a community sample, and (2) to verify the existence of social phobia subtypes in the community, and report on their relative prevalence, severity, and levels of impairment. METHODS: Community surveys were conducted contemporaneously in Winnipeg, Manitoba, and in Alberta, with a total of 1956 respondents. Instruments included the Comprehensive International Diagnostic Interview-Version 2.1 module for DSM-IV social phobia, enhanced with 6 additional (for a total of 12) social phobic situational probes to provide a more comprehensive assessment of possible subtypes, and additional questions about specific functional impairment due to social phobia. RESULTS: Of those persons in the community surveyed, most had no (60.4%) or few (ie, 1-3) (27.8%) social fears; few persons (3.4%) had many (ie, >/=7). Among those with DSM-IV social phobia (7.2%), classification based on number (normally distributed with median of 3, mode of 5) or content (eg, speaking-only vs other fears; performance-only vs interactional fears) of social fears failed to yield a defensible subtyping solution. Impairment increased linearly as the number of social fears was increased, with no clear threshold evident. CONCLUSIONS: Social phobia is associated with substantial impairment in multiple functional domains. Support for subtyping based on the extent or pattern of social fears was not provided. Rather, social phobia in the community seems to exist on a continuum of severity, with a greater number of feared situations associated with greater disability.

Public-speaking fears in a community sample. Prevalence, impact on functioning, and diagnostic classification.

BACKGROUND: Recent epidemiologic studies have revealed that social phobia is more prevalent than has been previously believed. An unresolved issue is the extent to which public-speaking fears constitute a recognizable form of social phobia in a community sample and, moreover, to what extent these fears are associated with functional morbidity. METHODS: To examine the prevalence and impact of public-speaking fears and their relationship to social phobia in a community sample, we conducted a randomized telephone survey of 499 residents of Winnipeg, Manitoba, a medium-sized midwestern metropolitan area. RESULTS: One third of the respondents reported that they had excessive anxiety when they spoke to a large audience. The onset of fears was early (ie, 50%, 75%, and 90% by the ages of 13, 17, and 20 years, respectively). Anxious cognitions about public speaking included the following fears: doing or saying something embarrassing (64%), one's mind going blank (74%), being unable to continue talking (63%), saying foolish things or not making sense (59%), and trembling, shaking, or showing other signs of anxiety (80%). In total, 10% (n = 49) of the respondents reported that public-speaking anxiety had resulted in a marked interference with their work (2%), social life (1%), or education (4%), or had caused them marked distress (8%). Twenty-three persons (5%) had public-speaking anxiety in isolation (ie, without evidence of additional kinds of social fears). CONCLUSIONS: These data support the inclusion of severe forms of public-speaking fears within the social phobia construct and, furthermore, suggest that public-speaking anxiety may have a detrimental impact on the lives of many individuals in the community.

Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207.

Prostate adenocarcinoma is the most common nonskin malignancy in males and the second most common cause of cancer death in the United States (Landis et al., 1998). Initial treatments of surgery or radiotherapy may cause impotence and/or incontinence from neural damage (Eastham and Scardino, 1998; Porter et al., 1998). When extraprostatic or metastatic disease develops, castration or pharmaceutical androgen ablation is utilized (Catalona, 1994). Androgen-resistant recurrence indicates a poor prognosis and justifies experimental chemotherapy (Oh and Kantoff, 1998). G207 (Mineta et al., 1995; Yazaki et al., 1995) is a multimutated herpes simplex virus 1 (HSV) vector that replicates within cancer cells, causing cellular death; however, replication is limited in normal cells, including those of the nervous system. In vitro, G207 at a low multiplicity of infection (MOI of 0.01) is oncolytic for multiple human prostate cancer cells. In athymic mice, a single intraneoplastic inoculation of G207 completely eradicates >22% of established subcutaneous human prostate cancer tumors irrespective of hormonal responsiveness. Two intraneoplastic inoculations of G207 completely eradicated two of three recurrent previously irradiated tumors and two intravenous administration of G207 induced tumor regression in distant subcutaneous tumors and completely eradicated one-fourth of the tumors.

Social phobia in adults with stuttering.

OBJECTIVE: The authors evaluated features of social anxiety in a group of adult stutterers to explore the soundness of the DSM-IV requirement that social phobia not be diagnosed in patients who stutter if their phobia relates to their stuttering. METHOD: They conducted diagnostic interviews and verbal fluency assessments with 16 consecutive adults seeking speech therapy for stuttering. Patients also completed scales measuring social phobia symptoms and associated disability. RESULTS: When DSM-IV criteria were modified to permit a diagnosis of social phobia if phobic symptoms were clearly excessive in relation to the severity of stuttering, seven of the 16 patients were given a diagnosis of social phobia. All seven identified social anxiety as an important source of role impairment. Three of the seven patients entered cognitive-behavioral group therapy and benefited from this intervention. CONCLUSIONS: Many adults seeking treatment for stuttering have salient difficulties with social anxiety that may prove amenable to cognitive-behavioral interventions. By precluding a diagnosis of social phobia in these patients, DSM-IV may hinder the identification of social anxiety as a source of disability and may limit access to treatment.

Setting diagnostic thresholds for social phobia: considerations from a community survey of social anxiety.

OBJECTIVE: The goal of this study was to gain a broader perspective on social anxiety in the community than has been achieved by epidemiologic surveys to date. METHODS: The authors conducted a telephone survey of social anxiety among 526 randomly selected respondents in a medium-sized Canadian city. RESULTS: Sixty-one percent of the respondents reported being much or somewhat more anxious than other people in at least one of the seven social situations surveyed. Speaking to a large audience (i.e., public speaking) was the most frequently feared situation (endorsed by 55.0% of the respondents), followed by speaking to a small group of familiar people (24.9%), dealing with people in authority (23.3%), attending social gatherings (14.5%), speaking to strangers or meeting new people (13.7%), and eating (7.1%) or writing (5.1%) in front of others. When the threshold for caseness was systematically modified--by altering the required level of psychosocial interference or distress or by including or excluding subjects with pure public speaking phobia--the rate of "social anxiety syndrome" in the community varied from 1.9% to 18.7%; 7.1% was the prevalence when the criteria were set to conform with DSM-III-R. CONCLUSIONS: Social anxiety is common in the community, but precise delineation of the prevalence of "social phobia" depends heavily on where the diagnostic threshold is set. If DSM-III-R criteria had been applied in previous epidemiologic studies, it is likely that those studies would have documented prevalences of social phobia that are several times as high as the currently accepted rates.

Obsessive-compulsive disorder in the community: an epidemiologic survey with clinical reappraisal.

OBJECTIVE: To examine the prevalence of obsessive-compulsive symptoms and DSM-IV obsessive-compulsive disorder (OCD), the authors conducted a telephone survey of 2,261 adults in four regions of Canada. METHOD: Trained lay interviewers administered a modified version of the OCD section of the Comprehensive International Diagnostic Interview. A subsample of respondents with probable cases and probable subclinical cases of OCD was then blindly reinterviewed by research personnel experienced in the assessment of OCD, using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale, to confirm the diagnosis and gauge the severity of OCD. RESULTS: The weighted 1-month prevalence of OCD in the entire sample according to the lay interviews was 3.1%. Upon clinical reappraisal, the 1-month prevalence estimate of OCD dropped to 0.6%; an additional 0.6% had subclinical OCD. The mean Yale-Brown Obsessive Compulsive Scale score of the individuals with OCD was 19.0 (SD = 4.6, median = 21); for those with subclinical OCD, the mean score was 15.4 (SD = 2.4, median = 14). Common reasons for overdiagnosis of OCD by the lay interviewers were inappropriate labeling of worries or concerns as obsessions and overestimating the degree of interference or distress attributable to obsessive-compulsive symptoms. CONCLUSIONS: OCD, while hardly a rare condition, may be somewhat less prevalent than had been believed on the basis of previous surveys. Additional studies are needed to substantiate these findings and to delineate precisely the extent of disability and reduced quality of life attributable to OCD (and OCD variants) in the community.

Panic disorder in patients attending a clinic for vestibular disorders.

In a study of the prevalence of panic and other anxiety disorders in persons with complaints of dizziness, 87 patients referred to a clinic for vestibular disorders completed self-rating measures of anxiety and depression; 32 also underwent a structured diagnostic interview. Thirteen (14.9%) of the patients met the DSM-III-R criteria for panic disorder, agoraphobia, or both. They rated themselves as much more disabled by their dizziness than the patients with no psychiatric disorder. Panic disorder was equally prevalent among patients with and without vestibular disease. In some cases panic disorder may provide an explanation for the dizziness, whereas in others it may be a comorbid condition compounding the disability attributable to the vestibular disorder.